2A25

Crystal structure of Siah1 SBD bound to the peptide EKPAAVVAPITTG from SIP

Summary for 2A25

• Entry DOI: 10.2210/pdb2a25/pdb
• Related: 1k2f 2a26
• Descriptor: Ubiquitin ligase SIAH1, Calcyclin-binding protein peptide, ZINC ION, ... (4 entities in total)
• Functional Keywords: protein-peptide complex, ligase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q8IUQ4; Nucleus: Q9HB71
• Total number of polymer chains: 2
• Total formula weight: 23013.68

Authors

Santelli, E.,Leone, M.,Li, C.,Fukushima, T.,Preece, N.E.,Olson, A.J.,Ely, K.R.,Reed, J.C.,Pellecchia, M.,Liddington, R.C.,Matsuzawa, S. (deposition date: 2005-06-21, release date: 2005-08-09, Last modification date: 2023-08-23)

Primary citation

Santelli, E.,Leone, M.,Li, C.,Fukushima, T.,Preece, N.E.,Olson, A.J.,Ely, K.R.,Reed, J.C.,Pellecchia, M.,Liddington, R.C.,Matsuzawa, S.
Structural Analysis of Siah1-Siah-interacting Protein Interactions and Insights into the Assembly of an E3 Ligase Multiprotein Complex
J.Biol.Chem., 280:34278-34287, 2005

PubMed Abstract: Siah1 is the central component of a multiprotein E3 ubiquitin ligase complex that targets beta-catenin for destruction in response to p53 activation. The E3 complex comprises, in addition to Siah1, Siah-interacting protein (SIP), the adaptor protein Skp1, and the F-box protein Ebi. Here we show that SIP engages Siah1 by means of two elements, both of which are required for mediating beta-catenin destruction in cells. An N-terminal dimerization domain of SIP sits across the saddle-shaped upper surface of Siah1, with two extended legs packing against the sides of Siah1 by means of a consensus PXAXVXP motif that is common to a family of Siah-binding proteins. The C-terminal domain of SIP, which binds to Skp1, protrudes from the lower surface of Siah1, and we propose that this surface provides the scaffold for bringing substrate and the E2 enzyme into apposition in the functional complex.

PubMed: 16085652
DOI: 10.1074/jbc.M506707200

Experimental method

X-RAY DIFFRACTION (2.2 Å)